ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • B St Pourcain, Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
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  • E B Robinson, Stanley Center for Psychiatric Research and Medical and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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  • V Anttila, Stanley Center for Psychiatric Research and Medical and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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  • B B Sullivan, Stanley Center for Psychiatric Research and Medical and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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  • J Maller, Analytic and Translational Genetics Unit, Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
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  • J Golding, Centre for Child and Adolescent Health, University of Bristol, Bristol, UK.
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  • D Skuse, Behavioural and Brain Sciences, Institute of Child Health, University College London, London, UK.
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  • S Ring, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom., Bristol Bioresource Laboratories, School of Social and Community Medicine, University of Bristol, Bristol, UK.
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  • D M Evans, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom., University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
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  • S Zammit, t MRC Centre for Neuropsychiatric Genetics and Genomics , Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University , Cardiff , UK.
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  • S E Fisher, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
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  • B M Neale, Department of Psychiatry, Laboratory for Neural Reconstruction, McLean Hospital, Harvard Medical School, Boston, MA, USA.
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  • R J L Anney, Department of Psychiatry, Laboratory for Neural Reconstruction, McLean Hospital, Harvard Medical School, Boston, MA, USA.
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  • S Ripke, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
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  • M V Hollegaard, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • T Werge, Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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  • A Ronald, Department of Psychological Sciences, Birkbeck University of London
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  • J Grove
  • D M Hougaard, i Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark ;
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  • A D Børglum
  • P B Mortensen, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark, National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark;, Centre for Integrative Sequencing, iSEQ, Aarhus University
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  • M J Daly, Stanley Center for Psychiatric Research and Medical and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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  • G Davey Smith, Bristol Bioresource Laboratories, School of Social and Community Medicine, University of Bristol, Bristol, UK.
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  • iPSYCH-SSI-Broad Autism Group

Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.Molecular Psychiatry advance online publication, 3 January 2017; doi:10.1038/mp.2016.198.

Original languageEnglish
JournalMolecular Psychiatry
Volume23
Pages (from-to)263-270
Number of pages8
ISSN1359-4184
DOIs
Publication statusPublished - 3 Jan 2017

    Research areas

  • GENOME-WIDE ASSOCIATION, AUTISTIC TRAITS, PSYCHIATRIC-DISORDERS, GENERAL-POPULATION, SPECTRUM, HERITABILITY, MUTATIONS, RISK, COGNITION, ETIOLOGY, Verbal Behavior/physiology, Humans, Male, Language, Social Behavior, Female, Child, Schizophrenia/genetics, Communication, Genome-Wide Association Study, Autism Spectrum Disorder/genetics, Risk Factors, Multifactorial Inheritance/genetics, Attention Deficit Disorder with Hyperactivity/genetics, Adolescent, Child Development Disorders, Pervasive/genetics, Longitudinal Studies

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